Glucagon sensitivity and clearance in type 1 diabetes: Insights from in vivo and in silico experiments

American Journal of Physiology - Endocrinology and Metabolism

Volumn 309, Issue 5, 2015, Pages E474-E486

  Hinshaw, Ling ^a   Mallad, Ashwini ^a   Man, Chiara Dalla ^b   Basu, Rita ^a   Cobelli, Claudio ^b   Carter, Rickey E ^a   Kudva, Yogish C ^a   Basu, Ananda ^a  

^a Mayo Clinic College of Medicine   (United States)

^b UNIVERSITY OF PADOVA   (Italy)

Author keywords

Endogenous glucose production; Glucagon; Type 1 diabetes

Indexed keywords

ADRENALIN; GLUCAGON; GLUCOSE; INSULIN; NORADRENALIN; GLUCOSE BLOOD LEVEL; HORMONE;

ADRENALIN BLOOD LEVEL; ADULT; AGED; ARTICLE; CLINICAL ARTICLE; COMPUTER MODEL; DOSE RESPONSE; FEMALE; GLUCAGON BLOOD LEVEL; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE CLAMP TECHNIQUE; GLUCOSE INFUSION; GLYCOGENOLYSIS; HORMONE SENSITIVITY; HUMAN; HYPOGLYCEMIA; IN VIVO STUDY; INSULIN BLOOD LEVEL; INSULIN DEPENDENT DIABETES MELLITUS; ISOTOPE DILUTION ASSAY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; NORADRENALIN BLOOD LEVEL; PRIORITY JOURNAL; ARTIFICIAL PANCREAS; COMPUTER SIMULATION; CONTROLLED STUDY; DRUG EFFECTS; LIVER; METABOLISM; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; YOUNG ADULT;

ADULT; BLOOD GLUCOSE; COMPUTER SIMULATION; DIABETES MELLITUS, TYPE 1; FEMALE; GLUCAGON; GLUCONEOGENESIS; GLUCOSE; GLUCOSE CLAMP TECHNIQUE; GLYCOGENOLYSIS; HORMONES; HUMANS; HYPOGLYCEMIA; LIVER; MALE; MIDDLE AGED; PANCREAS, ARTIFICIAL; YOUNG ADULT;

EID: 84940844094     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00236.2015     Document Type: Article

References (50)

1. Alford FP, Bloom SR, Nabarro JD. Glucagon metabolism in man, studies on the metabolic clearance rate and the plasma acute disappearance time of glucagon in normal and diabetic subjects. J Clin Endocrinol Metab 42: 830-838, 1976.
2. Bak MJ, Albrechtsen NW, Pedersen J, Hartmann B, Christensen M, Vilsboll T, Knop FK, Deacon CF, Dragsted LO, Holst JJ. Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans. Eur J Endocrinol 170: 529-538, 2014.
3. Basu A, Basu R, Shah P, Vella A, Johnson CM, Jensen M, Nair KS, Schwenk WF, Rizza RA. Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity. Diabetes 50: 1351-1362, 2001.
4. Basu A, Dalla Man C, Basu R, Toffolo G, Cobelli C, Rizza RA. Effects of type 2 diabetes on insulin secretion, insulin action, glucose effectiveness and postprandial glucose metabolism. Diabetes Care 32: 866-872, 2009.
5. Biava C, Grossman A, West M. Ultrastructural observations on renal glycogen in normal and pathologic human kidneys. Lab Invest 15: 330-356, 1966.
6. Bollen M, Keppens S, Stalmans W. Specific features of glycogen metabolism in the liver. Biochem J 336: 19-31, 1998.
7. Bowman RH. Gluconeogenesis in the isolated perfused rat kidney. J Biol Chem 245: 1604-1612, 1970.
8. Castle JR, Engle JM, El Youssef J, Massoud RG, Yuen KC, Kagan R, Ward WK. Novel use of glucagon in a closed-loop system for prevention of hypoglycemia in type 1 diabetes. Diabetes Care 33: 1282-1287, 2010.
9. Cersosimo E, Garlick P, Ferretti J. Abnormal glucose handling by the kidney in response to hypoglycemia in type 1 diabetes. Diabetes 50: 2087-2093, 2001.
10. Cersosimo E, Judd RL, Miles JM. Insulin regulation of renal glucose metabolism in conscious dogs. J Clin Invest 93: 2584-2589, 1994.
11. Cherrington AD, Chiasson JL, Liljenquist JE, Jennings AS, Keller U, Lacy WW. The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog. J Clin Invest 58: 1407-1418, 1976.
12. Cherrington AD, Liljenquist JE, Shulman GI, Williams PE, Lacy WW. Importance of hypoglycemia-induced glucose production during isolated glucagon deficiency. Am J Physiol Endocrinol Metab 236: E263-E271, 1979.
13. Deri JJ, Williams PE, Steiner KE, Cherrington AD. Altered ability of the liver to produce glucose following a period of glucagon deficiency. Diabetes 30: 490-495, 1981.
14. Dobbins RL, Connolly CC, Neal DW, Palladino LJ, Parlow AF, Cherrington AD. Role of glucagon in countering hypoglycemia induced by insulin infusion in dogs. Am J Physiol Endocrinol Metab 261: E773-E781, 1991.
15. Duckworth WC. Insulin and glucagon degradation by the kidney. II. Characterization of the mechanisms at neutral pH. Biochim Biophys Acta 437: 531-542, 1976.
16. Duckworth WC, Kitabchi AE. Insulin and glucagon degradation by the same enzyme. Diabetes 23: 536-543, 1974.
17. El-Khatib FH, Jiang J, Damiano ER. A feasibility study of bihormonal closed-loop blood glucose control using dual subcutaneous infusion of insulin and glucagon in ambulatory diabetic swine. J Diabet Sci Technol 3: 789-803, 2009.
18. El-Khatib FH, Jiang J, Gerrity RG, Damiano ER. Pharmacodynamics and stability of subcutaneously infused glucagon in a type 1 diabetic swine model in vivo. Diabet Technol Therap 9: 135-144, 2007.
19. El-Khatib FH, Russell SJ, Magyar KL, Sinha M, McKeon K, Nathan DM, Damiano ER. Autonomous and continuous adaptation of a bihormonal bionic pancreas in adults and adolescents with type 1 diabetes. J Clin Endocrinol Metab 99: 1701-1711, 2014.
20. El Youssef J, Castle JR, Bakhtiani PA, Haidar A, Branigan DL, Breen M, Ward WK. Quantification of the glycemic response to microdoses of subcutaneous glucagon at varying insulin levels. Diabetes Care 37: 3054-3060, 2014.
21. Foster JD, Nordlie RC. The biochemistry and molecular biology of the glucose-6-phosphatase system. Exp Biol Med (Maywood) 227: 601-608, 2002.
22. Haidar A, Legault L, Dallaire M, Alkhateeb A, Coriati A, Messier V, Cheng P, Millette M, Boulet B, Rabasa-Lhoret R. Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial. CMAJ 185: 297-305, 2013.
23. Hinshaw L, Dalla Man C, Nandy DK, Saad A, Bharucha AE, Levine JA, Rizza RA, Basu R, Carter RE, Cobelli C, Kudva YC, Basu A. Diurnal pattern of insulin action in type 1 diabetes: implications for a closed-loop system. Diabetes 62: 2223-2229, 2013.
24. Hornbuckle LA, Everett CA, Martin CC, Gustavson SS, Svitek CA, Oeser JK, Neal DW, Cherrington AD, O’Brien RM. Selective stimulation of G-6-Pase catalytic subunit but not G-6-P transporter gene expression by glucagon in vivo and cAMP in situ. Am J Physiol Endocrinol Metab 286: E795-E808, 2004.
25. Hwang JH, Perseghin G, Rothman DL, Cline GW, Magnusson I, Petersen KF, Shulman GI. Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study. J Clin Invest 95: 783-787, 1995.
26. Jacobs PG, El Youssef J, Castle JR, Engle JM, Branigan DL, Johnson P, Massoud R, Kamath A, Ward WK. Development of a fully automated closed loop artificial pancreas control system with dual pump delivery of insulin and glucagon. In: Conference Proceedings. Annual International Conference of the IEEE Engineering in Medicine and Biology. IEEE Eng Med Biol Soc Conf 2011: 397-400, 2011.
27. Kacerovsky M, Jones J, Schmid AI, Barosa C, Lettner A, Kacerovsky-Bielesz G, Szendroedi J, Chmelik M, Nowotny P, Chandramouli V, Wolzt M, Roden M. Postprandial and fasting hepatic glucose fluxes in long-standing type 1 diabetes. Diabetes 60: 1752-1758, 2011.
28. Lecavalier L, Bolli G, Cryer P, Gerich J. Contributions of gluconeogenesis and glycogenolysis during glucose counterregulation in normal humans. Am J Physiol Endocrinol Metab 256: E844-E851, 1989.
29. Lindsey A, Santeusanio F, Braaten J, Faloona GR, Unger RH. Pancreatic alpha-cell function in trauma. JAMA 227: 757-761, 1974.
30. Nielsen MF, Wise S, Dinneen SF, Schwenk WF, Basu A, Rizza RA. Assessment of hepatic sensitivity to glucagon in NIDDM: use as a tool to estimate the contribution of the indirect pathway to nocturnal glycogen synthesis. Diabetes 46: 2007-2016, 1997.
31. Orskov L, Alberti KG, Mengel A, Moller N, Pedersen O, Rasmussen O, Seefeldt T, Schmitz O. Decreased hepatic glucagon responses in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 34: 521-526, 1991.
32. Ramnanan CJ, Edgerton DS, Kraft G, Cherrington AD. Physiologic action of glucagon on liver glucose metabolism. Diabet Obes Metab 13, Suppl 1: 118-125, 2011.
33. Rivera N, Ramnanan CJ, An Z, Farmer T, Smith M, Farmer B, Irimia JM, Snead W, Lautz M, Roach PJ, Cherrington AD. Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs. J Clin Invest 120: 4425-4435, 2010.
34. Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care 35: 2148-2155, 2012.
35. Russell SJ, El-Khatib FH, Sinha M, Magyar KL, McKeon K, Goergen LG, Balliro C, Hillard MA, Nathan DM, Damiano ER. Outpatient glycemic control with a bionic pancreas in type 1 diabetes. N Engl J Med 2014.
36. Sherwin RS, Bastl C, Finkelstein FO, Fisher M, Black H, Hendler R, Felig P. Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon. J Clin Invest 57: 722-731, 1976.
37. Sherwin RS, Hendler R, DeFronzo R, Wahren J, Felic P. Glucose homeostasis during prolonged suppression of glucagon and insulin secretion by somatostatin. Proc Natl Acad Sci USA 74: 348-352, 1977.
38. Simonson DC, DeFronzo RA. Glucagon physiology and aging: evidence for enhanced hepatic sensitivity. Diabetologia 25: 1-7, 1983.
39. Starke A, Imamura T, Unger RH. Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration. J Clin Invest 79: 20-24, 1987.
40. Steele R, Wall JS, De Bodo RC, Altszuler N. Measurement of size and turnover rate of body glucose pool by the isotope dilution method. Am J Physiol 187: 15-24, 1956.
41. Steiner KE, Williams PE, Lacy WW, Cherrington AD. Effects of insulin on glucagon-stimulated glucose production in the conscious dog. Metab Clin Exper 39: 1325-1333, 1990.
42. Stekhoven DJ. Nonparametric Missing Value Imputation Using Random Forest. http://cran.r-project.org/web/packages/missForest/missForest.pdf. [4/23/2015].
43. Stekhoven DJ, Buhlmann P. Miss Forest—non-parametric missing value imputation for mixed-type data. Bioinformatics 28: 112-118, 2012.
44. Stumvoll M, Chintalapudi U, Perriello G, Welle S, Gutierrez O, Gerich J. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. J Clin Invest 96: 2528-2533, 1995.
45. Stumvoll M, Meyer C, Kreider M, Perriello G, Gerich J. Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. Metab Clin Exper 47: 1227-1232, 1998.
46. Stumvoll M, Meyer C, Mitrakou A, Nadkarni V, Gerich JE. Renal glucose production and utilization: new aspects in humans. Diabetologia 40: 749-757, 1997.
47. van Schaftingen E, Gerin I. The glucose-6-phosphatase system. Biochem J 362: 513-532, 2002.
48. Vella A, Reed AS, Charkoudian N, Shah P, Basu R, Basu A, Joyner MJ, Rizza RA. Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles. Am J Physiol Endocrinol Metab 285: E25-E30, 2003.
49. White NH, Skor D, Santiago JV. Practical closed-loop insulin delivery. A system for the maintenance of overnight euglycemia and the calculation of basal insulin requirements in insulin-dependent diabetics. Ann Intern Med 97: 210-213, 1982.
50. Zimliki C. The Content of IDE and PMA Applications for Artificial Pancreas Device Systems. Edited by US DHHS. Washington, DC: Food and Drug Administration, C2011.